15-32774126-G-A

Position:

• chr15-32774126-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277313.2(FMN1):​c.*184C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 604,430 control chromosomes in the GnomAD database, including 3,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (881 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3070 hom.)
• Consequence: FMN1 NM_001277313.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.958

Genes affected

FMN1 (HGNC:3768): (formin 1) This gene belongs to the formin homology family and encodes a protein that has a role in the formation of adherens junction and the polymerization of linear actin cables. The homologous gene in mouse is associated with limb deformity. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-32774126-G-A is Benign according to our data. Variant chr15-32774126-G-A is described in ClinVar as [Benign]. Clinvar id is 1233503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMN1	NM_001277313.2	c.*184C>T		3_prime_UTR_variant	21/21	ENST00000616417.5	NP_001264242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMN1	ENST00000616417.5	c.*184C>T		3_prime_UTR_variant	21/21	5	NM_001277313.2	ENSP00000479134	A2
FMN1	ENST00000334528.13	c.*184C>T		3_prime_UTR_variant	17/17	1		ENSP00000333950	P2
FMN1	ENST00000561249.5			downstream_gene_variant		5		ENSP00000453443	A2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15745 AN: 152020 Hom.: 881 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.112 AC: 50752 AN: 452292 Hom.: 3070 Cov.: 4 AF XY: 0.111 AC XY: 27122 AN XY: 243566

Gnomad4 AFR exome AF: 0.0644

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.0957

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.104 AC: 15755 AN: 152138 Hom.: 881 Cov.: 32 AF XY: 0.104 AC XY: 7769 AN XY: 74368

Gnomad4 AFR AF: 0.0689

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.121

Alfa AF: 0.111 Hom.: 284

Bravo AF: 0.103

Asia WGS AF: 0.118 AC: 408 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16958710; hg19: chr15-33066327; COSMIC: COSV57922398; COSMIC: COSV57922398;